A Fragment-Based Approach for the Development of G-Quadruplex Ligands: Role of the Amidoxime Moiety.

ABSTRACT: G-quadruplex (G4) nucleic acid structures have been reported to be involved in several human pathologies, including cancer, neurodegenerative disorders and infectious diseases; however, G4 targeting compounds still need implementation in terms of drug-like properties and selectivity in order to reach the clinical use. So far, G4 ligands have been mainly identified through high-throughput screening methods or design of molecules with pre-set features. Here, we describe the development of new heterocyclic ligands through a fragment-based drug discovery (FBDD) approach. The ligands were designed against the major G4 present in the long terminal repeat (LTR) promoter region of the human immunodeficiency virus-1 (HIV-1), the stabilization of which has been shown to suppress viral gene expressio

SUBMITTER: Tassinari M 

PROVIDER: S-EPMC6222391 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature